Tissue regeneration

Bone regeneration

The loss of a mandible due to cancer still poses a major challenge in our clinic. At present missing bone is substituted by autologous bone harvested from the patient. To avoid the morbidity, pain and an additional operation site involved by using autologous bone grafts our research focuses on the development of synthetic osteoconductive bone substitute materials and their combination with osteoinductive substances. Both principles: osteoconduction and osteoinduction are used from nature to facilitate bone regeneration. We want to apply the same two principles by developing a synthetic osteoconductive bone substitute material and combine it with osteoinductive bone morphogenetic proteins (BMP) so that major gaps in the mandible can be successfully bridged without the need to harvest bone from the ileac crest or to use the fibula of our patients.

Disc regeneration

The main objective of this EU funded project is to develop a biomimetic substitute used for disc regeneration. To that end, electro-spinning technology is exploited to develop a nano-fiber based, biocompatible, biodegradable, synthetic scaffold mimicking the mechanical properties of the native Nucleus Pulposus for immediate and short term treatment. The synthetic scaffold will be integrated with a bioactive-nano-polymer highly potent in supporting Nucleus Pulposus cells for long-term cure. In addition growth factors will be integrated into the material in a way so that their release suits the needs of this avascular site. Based on our experience with BMPs we have engineered and expressed BMP heterodimers to achieve appropriate binding and release characteristics.

Pulp regeneration

Tissue regeneration strategies have gained substantial attention in the dental literature over the recent years. Among the regenerative dental procedures, revascularization of a necrotic pulp space appears to be the treatment option that holds the most promise for the immediate future. The procedure is deemed to be especially helpful in children with teeth with incomplete root formation that lost pulp vitality due to caries or trauma. The goal of this project is to establish a new soft tissue in the pulp space that is capable of continuing hard tissue formation, thus rendering the tooth less prone to fracture and consequent loss. This project is based on our vast experience in hydrogels and growth factor delivery

Tooth regeneration

Cell-based tooth regeneration is an attractive approach that complements traditional restorative or surgical techniques for replacement of damaged dental tissues or tooth loss. Stem cells are characterized by their potential to self-replicate and their capacity to differentiate into a vast variety of cells populations. Stem cell populations are found in almost all adult human tissues and organs, including teeth. Adult stem cell populations are responsible for dental pulp and periodontium homeostasis and regeneration/repair. Mesenchymal stem cells isolated from deciduous and permanent teeth are tested for their potential applications in regenerative dentistry. Similarly, dental epithelial stem cells are isolated and used for recreating enamel. Induced pluripotent stem (iPS) technology is also applied for the regeneration of dental tissues. Several successful attempts have been made in our laboratories using stem cells from mice and rats for the regeneration of new brand entire teeth. We continue our targeted efforts for the regeneration specific dental tissues or entire teeth by applying novel technologies on stem cell imaging, selection and characterization. Innovative nanostructured materials are also used for stem cell tracking, gene and protein delivery, and formation of artificial stem cell niches in the regenerating teeth.

Research Staff

Thimios Mitsiadis, Prof. DDS, PhD

Lucia Jimenez-Rojo, Oberassistent, PhD

Anna Woloszyk, PhD candidate

Despoina Natsiou, PhD candidate

Innervation and neovascularization of regenerated tissues

Innervation plays a key role in the development, homeostasis and regeneration of organs and tissues of the orofacial complex. However, the mechanisms underlying these phenomena are not well understood yet. In particular, the role of innervation in tooth development and regeneration is neglected. To analyze the effects of innervation in tooth regeneration and in the fate and behavior of various stem cell populations we use microfluidic devices that allow long-term co-cultures of trigeminal neurons with tooth germs or dental stem cells.

Another important factor for the successful integration of stem cell-containing biomaterials is neovascularization to ensure sufficient oxygen and nutrient transport for the growth and survival of the integrated stem cells. We study neovascularization of the human dental stem cell-seeded 3D silk scaffolds on a chicken embryo chorioallantoic membrane (CAM) assay. Expression of markers for dental mesenchymal stem cells, endothelial cells and extracellular matrix components are under investigation.

Research Staff

Thimios Mitsiadis, Prof. DDS, PhD

Anna Woloszyk, PhD candidate

Pierfrancesco Pagella, PhD candidate