Influence of copper incorporation on structure and cell-type specific cytocompatibility of sol–gel-derived 13–93 bioactive glass for potential soft tissue applications

Abstract Copper (Cu²⁺)-containing silicate-based 13-93 bioactive glasses were synthesized via the sol–gel method to investigate their physicochemical properties and in vitro cytocompatibility. CuO contents ranging from 0.5 to 5 wt% were incorporated into 13-93 bioactive glass powders, which were characterized for particle size, structural integrity, and hydroxyapatite formation in simulated body fluid (SBF) and phosphate-buffered saline (PBS). Disc-shaped scaffolds were fabricated and tested on three distinct human cell lines: gastric adenocarcinoma (AGS), intestinal fibroblasts (HIF), and embryonic kidney epithelial cells (HEK-293). Cu²⁺ incorporation up to 5 wt% did not hinder hydroxyapatite formation, associated with reduced network connectivity. Cytotoxicity assays revealed a cell-type and concentration-dependent response, with HIF fibroblasts being most sensitive ( ≥1 wt% Cu²⁺), AGS cells exhibiting moderate tolerance, and HEK-293 cells maintaining stable viability across all optimized concentrations ( ≤1.5 wt%). Morphological observations of fibroblasts and AGS cells were consistent with the MTT assay results, indicating differences in cell viability under the tested conditions. These results highlight the critical importance of cell-type-specific evaluation when optimizing Cu²⁺ content for biomedical applications. Overall, Cu 2+ -containing 13-93 bioactive glasses demonstrate potential as therapeutic scaffolds for gastrointestinal tissue repair and ulcer treatment, with an optimal Cu²⁺ incorporation range of 0.5–1.5 wt% to ensure cytocompatibility across diverse cell types.