Currently, there is a huge gap from cell culture research results on the one hand (in vitro “models”) – to successful clinical applications on the other hand – (in vivo “patients”), which has reason:

(1) Physically, we can separate our bodies (tissues) into cellular and non-cellular components termed “The extracellular matrix” (ECM). (2) Our ECM however is a diversity of over 300 different proteins – with different functions – and only these complex interactions, together – can create “the magic of life”: Tissue. Organs. People.

Our ECM modulates a wide range of fundamental cellular behaviors in development, function and homeostasis of all eukaryotic cells. ECM gels fit to any three-dimensional space and can be delivered via minimally invasive surgical techniques. Hence, biomaterials extracted from naturally occurring ECM have received significant attention for potential therapeutic applications.

However, most used ECM in in vitro models are often single-component systems and harbour non-human (synthetic or animal material-based) components. Thus, their in vitro ability to mimic the actual in vivo diversity of human tissue is low. In addition, many xenogenic biomaterials are associated with immunological responses in patients, harbor the risk of xenogenic pathogen contamination and potential disease transmission. “We are evolutionarily related to animals, but in fact we are not animals!” Thus, the use of non-human ECM in clinical studies is controversially debated. Many xenogenic proteins are known to have a lower clinical performance when compared to human proteins. Hence, human ECM-biomaterials are a farsighted subject of patient safety!

In short: What is the best surrounding for our human cells for millions of years? The diversity of human non-cellular ECM proteins, of course!