Microengineered diabetic wound-on-a-chip model for emulating chronic wound dynamics.

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Tissue Engineering

Background:

• Diabetic wounds affect millions, presenting chronic, non-healing challenges and amputation risks.
• Existing 2D in vitro and animal models inadequately represent human diabetic wound complexity.
• A physiologically relevant model is crucial for understanding diabetic wound pathogenesis.

Purpose of the Study:

• To develop a humanized 3D diabetic wound-on-a-chip (DWOC) model.
• To simulate diabetic wound pathology under hyperglycemic conditions.
• To investigate cellular mechanisms and intercellular signaling in diabetic wound healing.

Main Methods:

• A four-channel microfluidic platform integrating dermal fibroblasts, macrophages, and endothelial cells in a collagen I/Matrigel matrix.
• Exposure to hyperglycemic conditions with advanced glycation end-products (AGEs) and lipopolysaccharide (LPS).
• Assessment of cellular viability, ECM remodeling, myofibroblast differentiation, angiogenesis, and cytokine profiles using immunofluorescence and biochemical assays.

Main Results:

• The DWOC model successfully replicated diabetic wound hallmarks: impaired ECM remodeling, disrupted cell crosstalk, and defective angiogenesis.
• Evidence of endothelial-to-mesenchymal transition (EndMT) in endothelial cells under diabetic stress was observed.
• Elevated pro-inflammatory cytokines and reduced anti-inflammatory/angiogenic factors confirmed the chronic inflammatory state.

Conclusions:

• The humanized 3D DWOC provides a physiologically relevant platform for studying diabetic wound healing.
• Endothelial-to-mesenchymal transition is identified as a critical pathological feature in diabetic wounds.
• This model facilitates preclinical evaluation of novel therapeutic strategies for diabetic wound treatment.