New 3D model to evaluate biomaterials for bone regeneration

There is a great need for bone replacement in dentistry and orthopedics. The current gold standard is what is known as autologous bone grafting. It involves taking healthy bone from a donor and implanting where needed in the same patient. However, the amount of bone that can be taken is limited, and there is a risk of infection. Therefore, other methods have been explored over the past 50 years. Some examples include collecting cells from a patient to grow them in a laboratory followed by their implantation, or creating support structures that contain biomaterials that can influence the behavior of the surrounding cells to regenerate tissues.

In his thesis, Luis Oliveros Anerillas and the research group he is part of used a set of commercially available hydrogels to create a laboratory-produced matrix where cells can attach and grow, and where the process of bone formation, osteogenesis, could be studied to be optimized for biomedical applications. He has used mesenchymal stem cells, MSCs, a type of stem cell found in adults that has the ability to self-renew and differentiate into other cell types, mainly to bone, fat and cartilage.

The first result of his thesis was that type I collagen was the optimal biomaterial among those tested for encapsulation of MSCs. In addition, it was found that a specific gene, MMP13, was highly expressed as a result of collagen encapsulation. This gene codes for an enzyme that breaks down the collagen matrix and has been linked to certain stages of osteogenesis.

The next outcome was the optimization of the differentiation protocols to replace animal-derived supplementation with platelet lysate, PLT. This is an important aspect because all applications of tissue-cultured grafts for human transplantation require strict rules to be adhered to where no xeno-derived, i.e. non-human, material may be used in transplantation.  The thesis shows that PLT is an ideal supplement to get the cells to replicate and proliferate, but PLT was inferior to the xeno-derived supplement for cell differentiation.

Finally, a silica calcium phosphate material, provided by a Swedish manufacturer, was tested, which was believed to be a powerful inducer of osteogenesis. It turned out that the material was osteogenic, non-inflammatory and that it caused MSCs to activate blood vessel formation, which may increase the potential clinical outcome of this biomaterial.

The entire thesis has been carried out in an in vitro environment, without animal experiments. MSCs from clinical isolates have been used, encapsulating them in a type I collagen matrix, studying how they differentiate into bone tissue and how this process can be optimized. The model can be used to reduce a large part of the animal experiments needed to evaluate potential biomaterials for bone regeneration applications.

Luis Oliveros Anerillas comes from Huesca, Spain. He holds a bachelor's degree in biology from the University of Alcalá de Henares, Madrid, and a master's degree in molecular biology from Umeå University.