According to popular estimates, the total length of our vascular system is enough to circle the equator twice. We did the math: for that to fit within the volume of the human body, the vessel “line” wrapping the Earth would have to be only a few micrometres thick. It sounds unbelievable, but in fact, most of the vessels in our body are incredibly small. That’s exactly what allows them to reach every corner of our body. A local supply network, so to speak.

But what happens when this network is damaged? At the Ludwig Boltzmann Institute for Traumatology (LBI Trauma), the research centre in cooperation with AUVA, a team led by Priv.-Doz. Dr. Wolfgang Holnthoner is exploring fundamental and forward-looking questions in vascular biology and regeneration.

Miniature Model Building: 3D Cultures and Organ-on-a-Chip

To accelerate the development and testing of new materials and ideas, researchers are turning to three-dimensional laboratory models. In these systems, cells – the smallest living units of the human body – are embedded in natural or synthetic scaffolds. This allows for a deeper understanding of processes such as inflammation, blood vessel formation, or tissue rejection.

Even more sophisticated are organ-on-a-chip technologies: tiny “organ systems” with microscale channels simulate blood or lymph flow and allow precise control over nutrients, pressure, and flow rate. These models enable real-time observation of how vessels grow, respond to drugs, or how diseases like atherosclerosis or lymphedema progress.

3D Printing and Bioprinting

Bioprinting goes a step further: here, a gel matrix containing living cells is used as “bio-ink.” In theory, entire microvascular networks can be built layer by layer, and one day perhaps even fully functional organs with integrated blood and lymphatic systems. While still largely a vision of the future, the first prototypes offer hope that functional tissue structures might one day be produced at the push of a button.

Cell-Free Vascular Grafts

An innovative approach is being pursued by Priv.-Doz. Dr. Karl Schneider at the Medical University of Vienna in his recently completed habilitation. He works with decellularized blood vessels, vessels stripped of all cells but retaining their structural framework. The concept: this natural scaffold could serve as a carrier that is gradually repopulated by the recipient’s own cells. This approach could replace artificial implants with biological material without needing to harvest vessels from elsewhere in the patient’s body. Removing the original cells also reduces the risk of rejection. Dr. Schneider began his research journey at LBI Trauma, and even after his move to MedUni Vienna, his connection to the institute remains strong.

Lymphedema & Co.: The Other Side of the Coin

While disruptions to the blood circulation often gain attention due to the life-threatening risks of heart attacks or strokes, problems in the lymphatic system are usually “just” chronic, yet they can severely impact quality of life. Lymphedema is a prime example: fluid buildup, swelling in limbs, inflammation, and infections are just some of the consequences. Disruptions in the blood system can also present chronically, such as in wounds that don’t heal due to poor oxygen supply.

More and more studies show that blood and lymphatic vessels work closely together. The lymphatic system produces about five litres of lymph fluid per day, essential for waste removal and immune function. When this system is impaired, it can negatively affect arteries too, for example, by promoting cholesterol build-up on vessel walls. The takeaway is clear: therapies that target only the blood vessels while neglecting the lymphatics are often incomplete.

Tiny Messages in a Bottle: Extracellular Vesicles (EVs)

A promising new research direction at LBI Trauma is now focusing specifically on the lymphatic system; via nanoscale “messages in a bottle” known as extracellular vesicles (EVs). These tiny vesicles transport molecular messages between cells. It has long been known that EVs from blood vessel cells change in disease states.

But what about EVs from lymphatic vessels? A recent study by Dr. Marianne Pultar and Johannes Oesterreicher, MSc, in the vascular biology group led by Dr. Holnthoner, set out to explore this. The result: certain molecular signals were found exclusively in lymphatic EVs: a clear distinction from their blood vessel counterparts. This knowledge could be key to precisely steering processes such as inflammation or tissue regeneration.

Targeted Stimulation of Lymphangiogenesis

Functional lymphatic vessels play a central role in healing. The team around Wolfgang Holnthoner plans to use these findings on EVs to specifically stimulate the growth of new lymphatic vessels, a process known as lymphangiogenesis. Their first step: to engineer EVs so they dock onto lymphatic vessels and promote new vessel formation. If successful, this could one day make it possible to treat chronic wounds, which are currently difficult to heal, much more effectively.