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.

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.

acute wounds, chronic wounds, MNB solution, MNB, Micro/nanobubbles, Micronanobubbles, negative pressure wound therapy with instillation

This is a pilot study that consists of 4 arms: Acute wounds: 1 control arm; 1 experimental arm (treated with MNB irrigation) Chronic wounds: 1 control arm; 1 experimental arm (treated with Negative pressure wound therapy with MNB instillation)

This is a double-blind, controlled study. Participants will be selected and matched based on similar wound profiles, pathology mechanisms, comorbidity profiles, and age. They will randomly be assigned to the experimental (MNB) or control (normal saline) group. The randomization ratio between both groups will be 1:1. Measurements of objective datapoints (e.g. StO2), cytokines, proteases, and pH will be taken by blinded research personnel.

This arm will include patients with acute wounds and will receive standard of care: irrigation with normal saline.

This arm will include patients with acute wounds and will receive experimental treatment: irrigation with micro/nanobubbles (MNB's) in normal saline.

This arm will include patients with chronic wounds and will receive standard of care: negative pressure wound therapy with instillation (NPWTi) using normal saline.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Qualifying individuals include participants that are readmitted to the hospital for the same wound that was treated by the study investigators.

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.

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.