Immunomodulatory Tissue-Engineering Strategies for Diabetic Foot Ulcer Management: A Systematic Review.

Area of Science:

• Bioengineering
• Regenerative Medicine
• Immunomodulation
• Diabetic Foot Ulcers (DFU)

Background:

• Diabetic Foot Ulcers (DFU) present a significant clinical challenge due to impaired wound healing and chronic inflammation.
• The immune microenvironment plays a critical role in DFU pathogenesis and resolution.
• Existing treatments often fall short, necessitating novel therapeutic strategies.

Purpose of the Study:

• To systematically review recent (2020-2025) bioengineering and regenerative medicine approaches targeting the DFU immune microenvironment.
• To evaluate the translational potential of these immunomodulatory strategies for clinical application in DFU management.

Main Methods:

• Systematic review adhering to PRISMA 2020 guidelines.
• Analysis of 34 studies focusing on immunomodulatory tissue-engineering strategies for DFU.
• Inclusion of studies utilizing various preclinical models (STZ-induced, db/db mice) and limited human data.

Main Results:

• Common strategies include hydrogels, nanofibers, microneedles, and dressings promoting M1 to M2 macrophage polarization.
• Therapies involving cytokine delivery, exosomes, nanozymes, metabolic reprogramming, and electrical stimulation demonstrated efficacy.
• These interventions reduced inflammation, enhanced angiogenesis, and accelerated wound closure by targeting key pathways (JAK/STAT, NF-κB, RAGE, HIF-1α).

Conclusions:

• Bioengineering and regenerative medicine offer promising immunomodulatory strategies for DFU.
• Preclinical data consistently show enhanced wound healing through macrophage polarization and inflammation resolution.
• Further well-powered clinical trials and personalized, biomarker-driven approaches are crucial for translation to patient care.