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Home / Modules / Angiogenesis

Angiogenesis

VEGF-driven vascular recovery replacing flat-rate perfusion repair with hypoxia-dependent angiogenesis.

Biology

Angiogenesis during wound healing is driven by the HIF-1alpha/VEGF signaling axis. When tissue oxygen drops below a threshold, hypoxia-inducible factor 1-alpha (HIF-1alpha) stabilizes and induces vascular endothelial growth factor (VEGF) production. VEGF stimulates endothelial cell sprouting from intact capillaries at the wound margin, gradually restoring perfusion to the wound bed. M2 macrophages also produce VEGF, coupling immune resolution to vascular repair.

Angiogenesis consumes VEGF proportionally, providing negative feedback that prevents excessive vessel growth. In diabetic wounds, HIF-1alpha is impaired (Thangarajah et al. 2009), reducing VEGF production and delaying vascular recovery.

Model

VEGF PDE: diffusion 0.08, decay 0.01. Two sources:

  • Hypoxia-driven: where O2 < vegf_hypoxia_threshold, VEGF is produced proportional to hypoxia severity (vegf_production_rate * (threshold - local_O2))
  • M2 macrophages: m2_vegf_rate per M2 macrophage per step

Perfusion modulation: replaces the flat angio_rate in the perfusion module with angio_vegf_rate * local_vegf * demand, where demand is the deficit from healthy perfusion.

VEGF consumption: angiogenesis consumes VEGF at vegf_consumption_rate * recovery, providing negative feedback.

Feedback loop:

Wound --> Destroyed vessels --> Low perfusion --> Low O2
                                                    |
                                HIF-1alpha --> VEGF production
                           (diabetic: impaired)     |
                                VEGF --> Endothelial sprouting --> Perfusion recovery
                                                    |
                                VEGF consumed (negative feedback)
                                                    |
                      M2 Macrophages --> VEGF (immune-vascular coupling)

Parameters

From modules/angiogenesis/config.toml:

Parameter Default Units Description Source
enabled true bool Master switch Convention
vegf_diffusion 0.08 - VEGF diffusion coefficient Calibrated
vegf_decay 0.01 per step VEGF natural decay Calibrated
vegf_production_rate 0.002 per step VEGF per hypoxic voxel Johnson & Wilgus 2014 (DOI)
vegf_hypoxia_threshold 0.5 normalized O2 for HIF-1alpha induction Schugart et al. 2008 (DOI)
vegf_consumption_rate 0.1 fraction VEGF consumed per unit recovery Calibrated
angio_vegf_rate 0.01 per step Perfusion recovery per unit VEGF Flegg et al. 2012 (DOI)
m2_vegf_rate 0.001 per step VEGF per M2 macrophage Jetten et al. 2014 (DOI)

Coupling

Reads

Field Source module How used
O2 tissue Hypoxia detection for VEGF production

Writes

Field Consumer modules What is written
VEGF perfusion (modulates recovery rate) VEGF concentration from hypoxia and M2 macrophages

Validation

Dataset Observable Sources Notes
angiogenesis_parameters VEGF dynamics, perfusion recovery coupling Catrina 2004, Thangarajah 2009, Jetten 2014 Parameter derivation

Literature data

Reference curves for validation (full citations in SOURCES.yaml):

Dataset File Normalization
VEGF kinetics vegf_kinetics.csv Peak = 1.0

Metrics

Column Units Description
mean_vegf_wound a.u. Mean VEGF in wound

Source files

File Purpose
vegf_pde.h VEGF diffusion field with hypoxia source
vegf_op.h VEGF-modulated perfusion recovery operation
config.toml Module configuration