Multimodality Therapy Shows Promise of “Therapeutic Advance” in Lower Extremity Wound Treatment
Summary: Vascular News reported on March 1, 2026 on a special communication published in the January 2026 issue of the Journal of Vascular Surgery: Venous and Lymphatic Disorders (JVS-VL) in which lead author Joann M. Lohr (William Jennings Bryan Dorn VA Medical Center, Columbia, USA) and colleagues present a comprehensive review of the mechanistic, translational, and clinical evidence supporting the combined use of pressurised intermittent topical oxygen (TWO2) therapy and non-contact cyclical compression as an integrative multimodality approach to lower extremity wound management. The central argument is that chronic wounds — including diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) — persist through a self-reinforcing cycle of tissue hypoxia, oedema, persistent inflammation, lymphatic dysfunction, ischaemia/reperfusion injury, bioburden, and tissue fibrosis. Most current interventions address only one or two of these drivers simultaneously, limiting efficacy. The proposed combination targets three key pathophysiological drivers concurrently: topical oxygen increases tissue oxygen tension, enhances microbial defence, promotes inflammation resolution through redox signalling and specialised pro-resolving mediator (SPM) synthesis, supports angiogenesis, and optimises collagen synthesis and ECM remodelling during tissue repair; while non-contact cyclical compression improves lymphatic clearance of inflammatory mediators, reduces oedema, restores perfusion, mitigates ischaemia/reperfusion injury, and activates mechanotransductive pathways supporting angiogenesis and tissue repair. Together, the authors argue, these modalities exert synergistic effects across multiple wound repair mechanisms, making the combination a potentially significant therapeutic advance. The review draws on a 2020 double-blinded RCT (Frykberg et al., Diabetes Care) showing 41.7% DFU closure at 12 weeks versus 13.5% in controls (p=0.004), with only 6.7% recurrence at 12 months versus 40% in controls; and a 132-patient prospective controlled study (Twafick et al., 2012) showing 76% versus 46% VLU healing (p<0.0001) with median time-to-closure of 57 versus 107 days. The TWO2 technology is marketed by AOTI Inc.; co-author Melodie M. Blakely is a clinical investigator for AOTI.
Key Highlights:
- Combination targets a “trifecta” of chronic wound drivers: tissue hypoxia, persistent inflammation, and lymphatic dysfunction — simultaneously, through two synergistic modalities
- Topical oxygen mechanism: raises wound tissue oxygen tension, enhances antimicrobial defence, drives SPM synthesis for inflammation resolution, supports angiogenesis and durable collagen crosslinking
- Cyclical compression mechanism: clears inflammatory mediators via lymphatic drainage, reduces oedema, restores microvascular perfusion, activates mechanotransductive repair pathways
- DFU RCT (Frykberg, Diabetes Care 2020): 41.7% closure at 12 weeks vs. 13.5% control (p=0.004); 56% vs. 27% at 12 months (p=0.013); 6.7% vs. 40% recurrence (p=0.070)
- VLU study (Twafick, 2012, n=132): 76% vs. 46% healing (p<0.0001); median time-to-closure 57 vs. 107 days; 6% vs. 47% recurrence at 36 months (p<0.0001)
- Authors conclude the integrative approach may “accelerate healing, enhance clinical outcomes, reduce complications, and achieve durable closure in difficult wounds of varied aetiologies” — framing it as adjunctive to current best practice standard wound care
Keywords: topical oxygen therapy wound, cyclical compression wound healing, multimodality wound treatment, venous leg ulcer treatment, diabetic foot ulcer oxygen, wound hypoxia lymphatic
Joann M. Lohr Melodie M. Blakely