Pearl powder, nacre, and nacre-derived water-soluble matrix (WSM) are natural mineral-organic materials with growing relevance for bone-regenerative research. Their biological activity appears to depend not only on calcium carbonate content but also on soluble matrix components that can influence osteoblast behavior, mineral deposition, and cellular stress responses. This narrative review compares pearl-specific osteogenic studies in cell, scaffold, and defect-repair models with selected comparator nanoparticle studies used to frame unresolved safety questions. The pearl-specific literature generally supports osteogenic activity, particularly in preosteoblast or osteoblast-lineage models and WSM-containing materials, but the evidence remains heterogeneous because species source, extraction method, particle size, release behavior, dose, and endpoint selection differ across studies. Evidence linking nano-pearl powder to autophagy-associated osteogenic differentiation is promising, especially in MC3T3-E1 models, but the existing pearl-specific literature provides limited direct evidence for high-dose toxicity, impaired autophagic flux, immunogenicity, heavy-metal-related risk, degradation-matched repair, or chronic biosafety. Future work should integrate material characterization, dose-response testing, oxidative and mitochondrial readouts, autophagic flux analysis, and osteogenic endpoints into a single experimental design. Such studies will be needed to define whether WSM-based or nano-pearl formulations can provide a reproducible and safe osteogenic window for bone-regenerative biomaterial development.
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