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Objectives and questions: Bioactive glass (BG) is widely used in bone regeneration due to its antimicrobial, angiogenic, osteostimulative, and osteoconductive properties. Its application in infected nonunions and large bone defects has increased over recent years. Despite encouraging outcomes, treatment failures still occur, and the underlying mechanisms remain not yet fully understood. This study aimed to investigate histomorphological characteristics and microRNA (miRNA) expression patterns in explanted BG samples from patients undergoing revision surgery due to BG malabsorption.

Material and methods: Malabsorbed BG samples (n=17) were collected during revision procedures. Corresponding clinical data, including patient demographics and microbiological findings, were recorded anonymously. For scanning electron microscopy (SEM) and X-ray spectroscopy (EDX), samples were fixed in glutaraldehyde with 2% phosphate buffer, dehydrated, carbon-coated, and imaged. X-ray spectroscopy was performed to assess calcium depositions. MiRNAs were isolated, transcribed, and analyzed per patient using qPCR arrays. In silico target prediction and bioinformatic pathway analyses were subsequently conducted.

Results: SEM and EDX demonstrated distinct histomorphological characteristics, including biofilm formation, bacterial exopolysaccharides, and reduced calcium deposition, corresponding with positive (infected) microbiological findings. MiRNA expression profiling and bioinformatic analyses revealed the upregulation of specific miRNAs associated with the humoral immune response in positive culture samples, including miR-150, -155, and -181b.

Discussion and conclusions: This study provides the first combined histomorphological and transcriptomic evaluation of malabsorbed bioactive glass. SEM and EDX revealed infection-associated features, including biofilm structures and bacterial extracellular matrix, alongside reduced calcium deposition. Concordant upregulation of humoral immune-related miRNAs further corroborated these results. The present study highlights the clinical relevance of low-grade, (occult) infections in bioactive glass treatment failure and underscores the need for careful patient-specific application of bioactive glass.