Amorphous titanium oxide (aTiO2) thin films biofunctionalized with CAP-p15 induce mineralized-like differentiation of human oral mucosal stem cells (hOMSCs).

Insufficient osseointegration of titanium-based implants is a factor conditioning their long-term success. Therefore, different surface modifications, such as multifunctional oxide coatings, calcium phosphates, and the addition of molecules such as peptides, have been developed to improve the bioactivity of titanium-based biomaterials. In this work, we investigate the behavior of human oral mucosal stem cells (hOMSCs) cultured on amorphous titanium oxide (aTiO₂), surfaces designed to simulate titanium (Ti) surfaces, biofunctionalized with a novel sequence derived from cementum attachment protein (CAP-p15), exploring its impact on guiding hOMSCs towards an osteogenic phenotype. We carried out cell attachment and viability assays. Next, hOMSCs differentiation was assessed by red alizarin stain, ALP activity, and western blot analysis by evaluating the expression of RUNX2, BSP, BMP2, and OCN at the protein level. Our results showed that functionalized surfaces with CAP-p15 (1 µg ml^-1) displayed a synergistic effect increasing cell proliferation and cell attachment, ALP activity, and expression of osteogenic-related markers. These data demonstrate that CAP-p15 and its interaction with aTiO₂surfaces promote osteoblastic differentiation and enhanced mineralization of hOMSCs when compared to pristine samples. Therefore, CAP-p15 shows the potential to be used as a therapeutical molecule capable of inducing mineralized tissue regeneration onto titanium-based implants.