Toward a novel tissue engineering method for repairing critically sized craniofacial bone defects
Hung, Ben Pen Jui
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Non-healing craniofacial bone defects are a major clinical problem. Tissue engineering has the potential to provide a next-generation solution, but specific focus on clinical translatable technologies is needed. A translatable approach combining using enhanced bone marrow and decellularized trabecular bone scaffolds is first investigated. The drawbacks of this approach, including difficulty of scaffold production and invasive cell harvesting, prompted the development of a new approach in which 3D printing of scaffolds is combined with adipose-derived stem cells signaled with platelet-derived growth factor BB. 3D printing was successfully used to create porous, anatomically shaped scaffolds with polycaprolactone. The lack of osteoinductive properties of polycaprolactone was addressed by development of a hybrid material consisting of bone extracellular matrix particles embedded in polycaprolactone and this material was demonstrated to be both printable and bioactive. Platelet-derived growth factor BB was examined as a suitable biomolecule for bone engineering by investigation of its osteoinductive effects on both marrow-derived and adipose-derived mesenchymal stem cells. Platelet-derived growth factor BB was found to be osteoinductive to adipose-derived but not to marrow-derived mesenchymal stem cells with both correlative and loss-of-function evidence, the latter of which made use of a reducible delivery vehicle developed specifically for siRNA delivery. Finally, the fate of transplanted cells is addressed by investigation of chemical exchange saturation transfer magnetic resonance imaging, found to be suitable for non-invasive and longitudinal in vivo monitoring.