Impaired Angiogenesis in Diabetic Wounds

Wound Physiology

Blood glucose 250 mg/dL

Wound hypoxia signal 80%

Simulation speed 1.0×

Angiogenic Response

HIF-1α stabilization

—%

Vessel density

Perfused connections

0 / 10

Days since injury

0.0

How it works

Endothelial "tip cells" sprout from the intact capillary at the wound margin and migrate up the VEGF concentration gradient secreted by hypoxic tissue at the wound bed — the same chemotactic process that builds new microvasculature during real wound repair.

HIF-1α stabilization: S = H · (1 − k·Gn),  k = 0.85 (0.20 on therapy)
Glucose term:         Gn = clamp((glucose − 90) / 310, 0, 1)
Hypoxia signal:       H  = hypoxia-slider value
Tip velocity:         v  = v0 · (0.25 + 0.75·S)
Branch probability:   Pb = b0 · S · dt   (per simulated day)

In normoxic tissue, prolyl-hydroxylase (PHD) enzymes use O₂ to mark HIF-1α for degradation; under hypoxia, PHD activity falls and HIF-1α accumulates, driving VEGF transcription. Chronic hyperglycemia keeps PHD activity abnormally high even when the tissue is hypoxic — HIF-1α is degraded almost as if oxygen were still plentiful (Botusan et al., PNAS 2008; Catrina & Zheng, Diabetologia 2016). The glucose term above models that pseudo-normoxic degradation: it suppresses HIF-1α, which throttles both VEGF output and VEGFR2-driven chemotactic sensitivity, so sprouts move slower, branch less, and rarely reach the wound center — the mechanistic basis of delayed diabetic wound healing.

Glucose slider — sets the glycemic suppression of HIF-1α stabilization.
Hypoxia signal — how ischemic the wound bed is (the raw drive HIF-1α would respond to at normal glucose).
PHD-inhibitor therapy — mimics drugs like roxadustat/DMOG that block PHD directly, bypassing the glucose effect and rescuing angiogenesis.
Green tips reached the wound center and perfuse it; red/orange tips are still actively sprouting.

Active sprout tip Perfused connection VEGF signal (wound center)

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Impaired Angiogenesis in Diabetic Wound Healing