Toward Developing Immunocompetent Diabetic Foot Ulcer-on-a-Chip Models for Drug Testing

Area of Science:

• Bioengineering
• Tissue Engineering
• Regenerative Medicine

Background:

• Diabetic foot ulcers (DFUs) affect millions globally, posing a significant health and economic burden.
• Current preclinical models (animal and in vitro) lack the physiological relevance needed for reliable DFU therapy testing.
• Existing models fail to adequately represent the complex pathophysiology of DFUs, leading to high clinical trial failure rates.

Purpose of the Study:

• To present key considerations for developing physiologically relevant, immunocompetent diabetic foot ulcer (DFU) models.
• To explore the potential of organ-on-a-chip (OoC) technology for modeling DFUs and testing topical therapies.
• To inform researchers on bioengineering strategies for creating robust DFU-on-a-chip platforms.

Main Methods:

• Bioengineering immunocompetent DFU-on-a-chip models using diseased cells from patients.
• Recapitulating the pathophysiological contribution of macrophages, fibroblasts, and keratinocytes in DFU models.
• Integrating diseased cells within reproducible scaffolds for endogenous extracellular matrix deposition and microfluidic platform incorporation.

Main Results:

• Proposed DFU-on-a-chip models incorporate diseased cells, scaffolds, and microfluidic systems for enhanced physiological relevance.
• These models aim to enable reliable drug testing for wound healing therapeutics.
• The development of immunocompetent DFU models is feasible for recapitulating stagnant inflammation characteristic of DFUs.

Conclusions:

• Organ-on-a-chip technology offers a promising avenue for creating physiologically relevant DFU models.
• Bioengineered immunocompetent DFU-on-a-chip models can improve the preclinical testing of topical therapies.
• These advanced models have the potential to reduce clinical trial failure rates for DFU treatments.