The Role of Negative Pressure Wound Therapy and Regenerative Approaches in Severe Pressure Ulcers

Pressure ulcers (PUs) represent a significant healthcare burden, affecting approximately 12.8% of hospitalized 
patients globally, with severe stage III and IV ulcers posing substantial therapeutic challenges. Traditional management 
strategies often prove insufficient for complex wounds, necessitating advanced treatment modalities. This comprehensive 
review examines the current evidence regarding negative pressure wound therapy (NPWT) and regenerative medicine 
approaches in the treatment of severe pressure ulcers, evaluating their mechanisms of action, clinical efficacy, safety profiles, 
and potential synergistic applications. A systematic literature search was conducted across PubMed, Cochrane Library, and 
international guideline databases, focusing on randomized controlled trials, systematic reviews, and clinical practice guidelines 
published between 2010 and 2026. NPWT demonstrates significant efficacy in promoting granulation tissue formation and 
reducing wound dimensions through mechanical forces, enhanced perfusion, and inflammatory exudate removal. Multiple 
randomized controlled trials confirm superior outcomes compared to conventional dressings, with 54% increased granulation 
tissue formation and reduced hospitalization rates. Regenerative approaches including mesenchymal stem cells, platelet-rich 
plasma, growth factors, and bioengineered skin substitutes show promising results as adjunctive therapies. Combination 
strategies, particularly NPWT with basic fibroblast growth factor or stem cells, demonstrate synergistic effects on wound 
healing parameters. NPWT represents an evidence-based modality for managing severe pressure ulcers when applied according 
to established protocols and contraindications. Emerging regenerative medicine approaches offer additional therapeutic 
options, particularly when combined with NPWT. Future directions include personalized medicine strategies, advanced 
biomaterials, and artificial intelligence-guided treatment algorithms to optimize outcomes in this challenging patient 
population.