Bioinorganics: synthetic growth factors for bone regeneration

Bone tissue is naturally able to regenerate when damaged. However, in many large defects caused by fractures due to aging or osteoporosis, trauma, tumor removal, etc., the natural regenerative ability of bone is not sufficient to fully heal the defect. In such cases, a graft is required to support the process of regeneration. While natural bone grafts, especially autografts, are widely applied in such conditions, their use is associated with important disadvantages. To overcome these limitations, a wide range of natural and synthetic alternatives has been developed, which are available off-the-shelf in large quantities. However, their clinical performance has always been considered inferior to that of autografts. Therefore, in the past decades, extensive research efforts have been invested in developing bone graft substitutes with improved properties and clinical performance. One of these strategies includes chemical modification of the existing bone graft substitutes with bioinorganics such as strontium (Sr2+), magnesium (Mg2+), zinc (Zn2+), etc. In this thesis, the effects of Sr2+, cobalt (Co2+) and fluoride (F-) were evaluated on the osteogenic differentiation of hMSCs. The results of these studies showed that cells might be influenced directly by the presence of the bioinorganics in their microenvironment, or indirectly through changes in the physicochemical properties of the CaPs, caused by the incorporation of bioinorganics into their structure. It was also shown that using cocktails of different bioinorganics might be an interesting strategy to affect different biological processes simultaneously. The effects of Co2+ ions incorporated into CaP coatings on vascularization were evaluated in an intramuscular goat model. The results showed that the presence of Co2+ in CaP coatings enhanced the new blood vessel formation and maturation, which in itself is considered beneficial in the process of bone regeneration. Finally, a model biomaterial based on polymer microspheres, to act as a carrier for bioinorganics was developed in this thesis. This simplified platform was successfully tested in vitro for screening direct effects of bioinorganics on hMSCs, independent of the properties of the carrier material.