Osteogenic Potential and Bone Matrix Maturity: Comparison of Demineralized Bone Matrix and P15 Polypeptide iFactor® in an In Vitro Study

<i>Background and Objectives:</i> Demineralized bone matrix (DBM) is a widely used bone graft substitute due to its osteoconductive and osteoinductive properties. However, its efficacy varies due to differences in donor, processing, and storage conditions. Synthetic alternatives, such as iFactor^®, combine non-organic bone mineral and a small peptide (P-15) to enhance the cellular attachment and osteogenesis. To compare the osteogenic potential and bone matrix maturity of iFactor^® and a commercial DBM scaffold through calcium nodule formation and Fourier transform infrared spectroscopy (FTIR) analysis. <i>Materials and Methods</i>: Human mesenchymal stem cells (hMSCs) were cultured and exposed to iFactor^® or DBM in paracrine culture conditions for 21 days. Calcium nodule formation was assessed using alizarin red staining and quantified spectrophotometrically. The FTIR analysis of hMSCs exposed to the scaffolds for three months evaluated the biomolecular composition and bone matrix maturity. <i>Results</i>: Calcium nodules formed in both groups but in smaller quantities than in the positive control (<i>p</i> < 0.05). The biomolecular components of the DBM were similar to healthy bone (<i>p</i> > 0.05) than those of the iFactor^® group (<i>p</i> < 0.005). A different rate of bone regeneration was observed through the formation of a greater number of calcium nodule aggregates identified in the extracellular matrix of mesenchymal stem cell cultures exposed to iFactor^® compared to those cultures enriched with DBM. <i>Conclusions</i>: Both experimental matrices demonstrated similar osteogenic potential at the 3-month follow-up. Although DBM has a closer biomolecular composition and carbonate substitution compared to healthy bone, iFactor^® showed faster matrix maturity expressed through the formation of a greater number of calcium nodule aggregates and higher hMSCs proliferation.