Enhanced cellular viability and osteogenic activity in oxygen-self-generating and magnetically responsive alginate microgels as advanced cell carriers

Improving the accuracy of in vitro three-dimensional (3D) cellular cultures more closely replicates the in vivo microenvironment by mimicking the complex tissue structures, enhancing cell-cell interactions, and increasing differentiation potential along with functional capabilities. Natural materials aid in cell adhesion and proliferation within the 3D matrix, providing a more realistic growth environment. Oxygen availability is also critical for cell survival in 3D cultures, as a lack of oxygen can impede proliferation, reduce functionality, and ultimately result in cell death. To address the issue of oxygen supply in such systems, a novel magnetic alginate-based microcarrier that generates oxygen autonomously has been developed. This microcarrier contains calcium peroxide encapsulated within polylactic acid microspheres (CP), which act as an internal oxygen reservoir. The release of calcium ions results in weak interactions with alginate, thus improving structural integrity while also supporting bone marrow stromal cells (BMSCs) and creating a more in vivo-like microenvironment. Notably, when exposed to an external magnetic field, BMSCs on these CP/Fe₃O₄/SA microcarriers show improved viability, a marked decrease in hypoxia-inducible factor-1α (HIF-1α), and increased osteogenic gene expression. Therefore, the CP/Fe₃O₄/SA microcarriers represent a promising approach for enhancing in vitro 3D culture methods and offer significant potential for tissue repair and regeneration.