3D-Printed Composite Scaffolds Containing SiO₂ for Bone Regeneration in In Vivo Models: A Systematic Review

Bone fractures are a growing global burden due to population aging and increasing osteoporosis incidence, leading to impaired healing and a demand for advanced regenerative strategies. Three-dimensional (3D) printed scaffolds have emerged as promising biomaterial platforms owing to their ability to mimic native bone architecture and deliver bioactive cues. Among the bioactive components explored, silica (SiO₂) has been shown to modulate osteoblast proliferation, promote angiogenesis, and enhance mineralized matrix deposition when incorporated into calcium- and phosphate-containing biomaterials. This systematic review aimed to evaluate 3D-printed composite scaffolds containing SiO₂ used in in vivo bone defect models, focusing on their biological performance and regenerative outcomes based on studies retrieved from PubMed, Scopus, Embase, and Web of Science published between 2005 and 2025. It is important to emphasize that this review focuses on composite biomaterial systems in which SiO₂ is incorporated as a bioactive component, rather than on structurally pure SiO₂-containing composite scaffolds. The included reports demonstrated that both synthetic and biogenic SiO₂ modulate key scaffold characteristics, including porosity, surface topography, wettability, and degradation behavior. Architectures with interconnected pores ranging from 200 to 600 μm, increased surface roughness, and improved hydrophilicity facilitated protein adsorption and cell adhesion, while variations in particle morphology and crystallinity influenced ion release kinetics and osteogenic signaling. In vivo studies conducted mainly in rodent and rabbit critical-sized defect models consistently showed enhanced bone formation in SiO₂-containing scaffolds, as demonstrated by Micro-CT analysis, histomorphometry, and the expression of osteogenic markers. Additionally, SiO₂-containing scaffolds were shown to modulate local inflammatory responses and upregulate osteogenic gene expression, particularly when combined with calcium phosphate phases. Overall, SiO₂-functionalized 3D-printed scaffolds represent a promising strategy for bone tissue engineering when combined with calcium phosphate phases, due to their synergistic effects on surface bioactivity, osteogenic signaling, and bone regeneration.