3D-printed Mechanically Strong Calcium Phosphate Cement Scaffold with Metformin/Stem Cell-encapsulating Alginate Microbeads for Bone Tissue Engineering

The utilization of Calcium Phosphate Cement (CPC) is limited due to its low mechanical strength and difficulty to seed cells deep into the scaffold. The objectives of this study were to: (1) develop a 3D-printed CPC-dopamine-metformin scaffold encapsulating human periodontal ligament stem cells (hPDLSCs), (2) investigate the effect of dopamine on the performance of CPC, and (3) evaluate the effect of microbead degradation and metformin release on the osteogenic differentiation of the released hPDLSCs. The mechanical property of the CPC scaffolds was elevated by adding dopamine, and the CPC scaffold with 7 wt.% dopamine had the highest compressive strength (7.35 MPa). Four types of microbeads with different content of alginate (oxidized alginate), hPDLSCs, and 2% metformin were fabricated. Morphological and cell counting kit tests confirm that the hPDLSCs are protected by microbeads encapsulation during the CPC setting process. The alkaline phosphatase test indicates that the osteogenic differentiation of hPDLSCs was enhanced by the fast release of cells and metformin. The microbeads consisting of 2% oxidized alginate and 2% metformin were optimal for cell delivery due to favorable cell release and osteogenic differentiation. This CPC scaffold is promising used for bone regeneration in dental, craniofacial, and orthopedic applications.