How We Grow Blood Vessels in the Laboratory
From Science to Life-Saving: The Art of Providing Tissues with Blood Supply
Imagine being able to grow human tissue in the laboratory - for transplants, without waiting lists or rejection reactions. But there is a crucial problem: Without blood vessels, any artificial tissue dies within a very short time. The supply of oxygen and nutrients is vital, as is the disposal of waste products. This is where angiogenesis comes into play - the process of forming new blood vessels from existing ones. In tissue engineering, it is the biggest hurdle and at the same time the holy grail for successful implantations 5 7 .
Supply oxygen and nutrients while removing waste products
Angiogenesis is a complex biological process in which endothelial cells (the inner lining of blood vessels) sprout from existing vessels and form new capillaries. This process is controlled by growth factors such as VEGF (Vascular Endothelial Growth Factor), FGF (Fibroblast Growth Factor), and PDGF (Platelet-Derived Growth Factor) 2 5 .
Endothelial cells are activated by growth factors
Breakdown of the basement membrane
Endothelial cells move and multiply
Cells form tubular structures
Recruitment of pericytes and smooth muscle cells
Without spatial and temporal control of growth factors, disorganized, leaky vessels form - similar to those in tumors 7 .
Biomaterials such as Alginates, Fibrin, and Hydrogels form the scaffold for vascular formation. They mimic the extracellular matrix (ECM) and can release growth factors 1 9 .
Natural polymers with high biocompatibility that serve as carriers for endothelial cells or growth factors 1 .
Water-filled networks that provide a 3D environment for cells and mimic the ECM 9 .
Can mimic hypoxia (oxygen deficiency) and promote the expression of angiogenic genes via HIF-1α 6 .
| Material | Properties | Application in Angiogenesis |
|---|---|---|
| Alginates | Biocompatible, biodegradable | Carrier for cells/growth factors |
| Hydrogels | ECM-like, customizable | 3D cell culture, vessel formation |
| Cobalt-modified | Mimics hypoxia, stabilizes HIF-1α | Promotion of VEGF expression |
To study angiogenesis in the laboratory, researchers developed a 3D in vitro model with fibrin beads 2 .
Microcarriers (beads) are coated with human endothelial cells (HUVECs)
The beads are embedded in a fibrin gel that serves as an ECM substitute
A layer of fibroblasts secretes growth factors
Addition of platelet-based preparations (PRP, PRP-HA or platelet lysates)
After 48 hours, the formed capillaries are analyzed microscopically and morphometrically 2
PRP (Platelet-Rich Plasma) and PRP-HA (with hyaluronic acid) induced the best angiogenic response, including orderly tube formation. Platelet lysates promoted proliferation but no orderly vessel formation. Hyaluronic acid improved the controlled release of growth factors 2 .
| Preparation | Concentration | Effect on Endothelial Cells |
|---|---|---|
| PRP | 5-40% | Orderly tube formation, anti-aging effect |
| PRP-HA | 5-40% | Optimized release, better maturation |
| Platelet lysates | 5-40% | Uncontrolled proliferation |
| Parameter | PRP-treated | Platelet lysate-treated |
|---|---|---|
| Vessel length (μm) | 250 ± 30 | 180 ± 25 |
| Branching points | 15 ± 3 | 8 ± 2 |
| Lumen formation | Yes | No |
The following materials are essential for angiogenesis research:
The future of angiogenesis research lies in the combination of biomaterials with biophysical stimuli (e.g., electrical stimulation, ultrasound) 3 as well as in personalized medicine through bioinformatics 4 . The goal is to grow functional vascular networks that connect with the host and keep large tissue constructs alive.
Angiogenesis research in tissue engineering has made enormous progress - from simple 2D cell cultures to complex 3D models with precise control over growth factors. However, the biggest challenge remains the transfer to the clinic. With new biomaterials, improved delivery systems, and biophysical stimuli, it may soon be possible to grow fully functional tissues in the laboratory 7 9 .