Large bone defects, such as those resulting from tumor excision, critical size defect fractures, or non-union, remain a clinical problem in bone reconstructive surgery. Current treatments involving autologous or allogenic bone grafts present the problem of implant availability and quality, or associated infection and immune response risks, respectively. In addition, as bone formation is highly dependent on the presence of osteogenic cells at the implant site, vascularization is also a major concern, as inadequate bone vascularization is typically associated with decreased bone formation, tissue necrosis, and implant integration failure, leading to impaired bone repair. The bone biology focus area mainly aims to study the cellular mechanisms involved in the different phases of bone healing and their interplay for a better understanding and further monitoring of the process.
The induction of vessels within an artificial bone substitute, by co-seeding endothelial progenitors and mesenchymal stromal cells, might improve the vascularization of the graft. We are investigating the use of microfluidic systems to enhance the development of a vascular environment, while assessing the role of angiogenic factors on vascular sprouting and maturation.
Mechanical in-/stability is known to influence the bone healing path (direct versus indirect bone healing) and callus formation in vivo. Indirect bone healing results in successive events including inflammation, recruitment and differentiation of stem cells, the formation of a cartilaginous callus that will remodel to restore the bone biological and structural integrity. Using a newly developed bone bioreactor we are investigating in more details the role of the mechanical environment on stem cell differentiation fate in vitro.
The role of the immune system in guiding and directing the healing response is gaining in importance and this area of osteoimmunology is an exciting new field of research. We are investigating how modulation of immune cell responses may be used to enhance the bone healing process, as well as assessing the potential of immune cell characterization to be used as a predictive marker of individual patient healing potential in a personalized medicine approach.