Aspiration-assisted freeform bioprinting of mesenchymal stem cell spheroids within alginate microgels.

Aspiration-assisted freeform bioprinting (AAfB) has emerged as a promising technique for precise placement of tissue spheroids in three-dimensional (3D) space enabling tissue fabrication. To achieve success in embedded bioprinting using AAfB, an ideal support bath should possess shear-thinning behavior and yield-stress to facilitate tight fusion and assembly of bioprinted spheroids forming tissues. Several studies have demonstrated support baths for embedded bioprinting in the past few years, yet a majority of these materials poses challenges due to their low biocompatibility, opaqueness, complex and prolonged preparation procedures, and limited spheroid fusion efficacy. In this study, to circumvent the aforementioned limitations, we present the feasibility of AAfB of human mesenchymal stem cell (hMSC) spheroids in alginate microgels as a support bath. Alginate microgels were first prepared with different particle sizes modulated by blending time and concentration, followed by determination of the optimal bioprinting conditions by the assessment of rheological properties, bioprintability, and spheroid fusion efficiency. The bioprinted and consequently self-assembled tissue structures made of hMSC spheroids were osteogenically induced for bone tissue formation. Alongside, we investigated the effects of peripheral blood monocyte-derived osteoclast incorporation into the hMSC spheroids in heterotypic bone tissue formation. We demonstrated that alginate microgels enabled unprecedented positional accuracy (∼5%), transparency for visualization, and improved fusion efficiency (∼97%) of bioprinted hMSC spheroids for bone fabrication. This study demonstrates the potential of using alginate microgels as a support bath for many different applications including but not limited to freeform bioprinting of spheroids, cell-laden hydrogels, and fugitive inks to form viable tissue constructs.

Comparative effects of controlled release of sodium bicarbonate and doxorubicin on osteoblast and osteosarcoma cell viability.

This study intends to analyze the effects of doxorubicin and sodium bicarbonate release with polycaprolactone (PCL) coating on calcium phosphate system which is a bone like material, on the cell viability and proliferation of osteosarcoma and osteoblast. Increased systematic pH concentrations locally by the release of sodium bicarbonate diminished acidosis and hence, alleviated malignancy. In our studies, we have shown that the same of dosage of doxorubicin inhibited both osteoblast and osteosarcoma cell attachment and viability whereas, sodium bicarbonate abated osteosarcoma cell proliferation. Sodium bicarbonate also inhibited osteoblast cell proliferation in the early time points, however, the cell viability increased after the initial burst release of the molecule. Polymer coating on calcium phosphate-based implants, as carriers of drug, can minimize chances of toxic effects of higher oral drug dosage in the body, and also help in delivering effective doses of drugs, locally to the target tissues, as compared to the oral drug delivery approach. A coating of PCL was thus incorporated to control the initial burst release of bicarbonate, which enhanced the osteoblast cell viability, but was capable of diminishing osteosarcoma cell proliferation. The novelty and clinical significance of this study lies in the understanding of unique delivery using encapsulated naturally occurring and more benign sodium bicarbonate, for usage after excision of the cancerous bone, without any adverse effects on normal bone cells.