Bone regeneration by scaffold-free, prevascularized tissue constructs from microvascular fragment isolates of adipose tissue

• Applicant: Professor Dr. Matthias W. Laschke, Ph.D.
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: since 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 318765517

The aim of this project is to use adipose tissue as clinically attractive tissue source for the fabrication of prevascularized tissue constructs for bone regeneration. For this purpose, scaffold-free, three-dimensional spheroids are generated from microvascular fragment isolates. The stem cells within these spheroids are chondrogenically differentiated in vitro to ideally promote bone regeneration in vivo via the process of endochondral ossification. In doing so, the functionality of the integrated microvascular fragments shall be preserved to improve the blood perfusion and regenerative potential of the spheroids. Freshly generated microvascular fragment spheroids with non-differentiated or osteogenically differentiated stem cells as well as non-prevascularized spheroids, which solely consist of stem cells, serve as controls. The different spheroid types are characterized in vitro in terms of their morphology, cellular composition, viability, proliferation, differentiation and angiogenic activity. In addition, their vascularization capacity and bone regenerative potential are analyzed in vivo in the dorsal skinfold chamber model and in a murine non-union model. In this way, a novel microvascular fragment-based treatment strategy for bone regeneration is established, which combines promising concepts from our own prior work and the current state of bone tissue engineering research.

• DFG Programme: Research Grants