Collagen is an ancient building block for life that makes a broad variety of tissues. Conversation with the collagen expert Dr. Lothar Schlösser, Head of Geistlich Material Discovery Research, on the successful use of collagen in regenerating bones, cartilage and skin.
Dr. Schlösser, where would our body be without collagen?
Dr. Schlösser: Nearly one third of endogenous proteins are made from collagen. Without this building material we would be nothing. To begin with, we would be completely permeable and a cluster of cells devoid of form, because everywhere, where boundaries are required or where protected spaces need to be created, collagen is used in the body. Secondly, no bone could maintain itself without collagen. Our skeleton would be far too brittle, and we would immediately collapse. Bones possess strength and a certain flexibility because of collagen reinforcement. And thirdly, collagen is vital for providing structure. In the area between cells, collagen is the predominant protein conducting tissue formation. It provides a type of construction manual.
Collagen also seems to be a model for evolutionary success…
Dr. Schlösser: Yes, collagen is far older than bone. Collagen was found in primordial and primitive organisms, such as fresh water polyps, jellyfish and sponges. But even as evolution progressed and bone appeared, collagen continued to be an essential building material.
Nature tinkered with this material in the course of evolutionary history and tried it out in a wide range of areas and functions. This resulted in many extremely useful applications in our body, typically in conjunction with other materials, such as in the combination of collagen and bone.
You make use of this link in bone regeneration.
Dr. Schlösser: That’s right. If I want to build up bone in order to fix dental implants, I need to shield the area for a while. This requires a collagen membrane that is sufficiently impermeable to prevent soft tissue cells from growing into the bony defect. Bone cannot be formed in sites where soft tissues are found.
The membrane is permeable in spite of this barrier function. It permits, for example, nutrients to be exchanged and some communication between the spaces. We therefore have a reliable impediment to soft tissue cells such as fibroblasts, but not complete impermeability.
To what extent is it possible to influence the raw material collagen, to shape it to a required form?
Dr. Schlösser: Considerably. We want to provide the body with a processed raw material characterized by a very specific organization and architecture. To accomplish this, we partly disassemble the bundles of collagen fiber into their component parts and reassemble them, so to speak, by means of freeze-drying. Depending on how this freezing process is controlled, we end up with bigger or smaller ice crystals. Bigger ice crystals produce larger pores, and smaller crystals smaller ones. For membranes with a barrier function, the collagen is not divided but left with its natural organization and architecture.
There is a big need for skin regeneration worldwide. Do Geistlich collagens play a role?
Dr. Schlösser: We don’t have any approved products for these indications, yet. However, a clinical study has been started employing collagen matrices for maxillofacial surgery. It has to do with skin regeneration in the facial area, such as after surgically removing so-called basaliomas, which are tumors that chiefly develop in facial regions with exposure to the sun, such as the forehead, nose or ears. The prevalence has increased a lot in recent years. Many of them have to be excised.
If you leave such a wound to heal on its own, scarred and indented tissue forms, which can be disfiguring, particularly in the face. So far there has not been anything that restores the tissue without leaving a disfigurement. An ingenious collagen matrix system can fill the defects and, as our preliminary data shows, provide good skin regeneration.
Other parts of the body also need “repairing”…
Dr. Schlösser: Yes, knees, for instance. Sports can involve painful cartilage injuries. The AMIC® technique removes part of the damaged cartilage, and the bone beneath it is drilled so that it can bleed into the defect and allow new tissue to form. A suitable collagen membrane is placed over the defect, and provides a protected area in which the tissue can regenerate.
And it works?
Dr. Schlösser: It does, indeed! This operation is relatively complex – but not, for example, compared to the ACI technique, which requires chondrocytes to be cultivated – but it works.
But normally the body repairs itself…
Dr. Schlösser: That is the point. Ultimately, we are just giving nature a little leg up. A body wants to regenerate. But to do so, nature needs protected spaces and assembly instructions that it does not always have.
If we provide a matrix and a safe “zone of tranquility,” the body will have a much easier task regenerating specific structures. We are empowering the body.
Does the body ever say, “I don’t want your help” and reject the material?
Dr. Schlösser: Collagen is very old and preserved genetically across various species. That is, with just a few small exceptions, it is the same building material in all mammals. If collagen is processed well – and this is where Geistlich of course comes in with its expertise – it does not cause immunological reactions. The very rare cases of a collagen allergy are special exceptions.
What needs to be considered?
Dr. Schlösser: The raw material has to be processed very conscientiously and cleanly. It is crucial to stabilize the material.
Collagen is able to store a great deal of water. But this characteristic can destabilize the structure.
Nature helps itself by cross-linking molecules that stabilize the material. If you use processes that weaken the collagen scaffold it then has to be cross-linked to be restabilized. If you cannot control this artificial cross-linking, tissue integration and inflammation can become problems.
Geistlich has been researching and working with collagen as a company for many decades. Do you believe this material still harbors secrets?
Dr. Schlösser: Collagen is extremely versatile; there is still much that we don’t know. Although I have been involved with collagen for a very long time, the material still surprises and fascinates me on a regular Basis.