Osseointegration is vital to success in orthopedic and dental reconstructions with implanted materials. The bone matrix or cells—particularly osteoblasts—are required to achieve functional contact on the implant surface. Osteoblast induction is therefore essential for osteogenesis to occur. Enhancement of osteoblast adhesion, proliferation, and differentiation, particularly by implant surface modifications, have been found challenging to develop. Secretory Leukocyte Protease Inhibitor (SLPI), a cation ionic protein with anti-inflammatory and anti-bacterial activities, showed activation in osteoblast proliferation and differentiation. However, the effects of coating recombinant human (rh) SLPI on a titanium alloy surface on human osteoblast adhesion, proliferation, and differentiation has never been investigated. In this study, titanium alloys (Ti–6Al–4V) were coated with rhSLPI, while human osteoblast adhesion, proliferation, differentiation, actin cytoskeletal organization, and gene expressions involved in cell adhesion and differentiation were investigated. The results indicate that coating titanium with 10–100 µg/ml rhSLPI enhanced the physical properties of the Ti surface and enhanced human osteoblast (hFOB 1.19) cell adhesion, activated actin dynamic, enhanced adhesive forces, upregulated integrins α1, α2, and α5, enhanced cell proliferation, mineralization, alkaline phosphatase activity, and upregulated ALP, OCN, and Runx2. This is the first study to demonstrate that coating SLPI on titanium surfaces enhances osseointegration and could be a candidate molecule for surface modification in medical implants.

The clinical success rate of titanium (Ti) implants is significantly reduced in elderly patients and by implant-associated bacterial infections. Thus, Ti surfaces were modified using sandblasted large-grit alkaline etching (SLA), argon-nonthermal plasma treatment, and recombinant human secretory leukocyte protease inhibitor (rhSLPI) coating. This study evaluated surface characteristics, human fetal osteoblast (hFOB 1.19) activities, and antibacterial efficacy. The modified surfaces exhibited increased roughness and hydrophilicity compared to Ti. The SBPTi-rhSLPI enhanced 7-day protein retention on the surface. While Ti promoted higher cell proliferation, the modified groups demonstrated superior cell adhesion and mineralization. Specifically, SBPTi-rhSLPI showed the highest cytoplasmic spreading, adhesion-related gene expression (Itg$\alpha$1, Itg$\alpha$2, Itg$\alpha$5, and Itg$\beta$1), and mineralization. Additionally, rhSLPI-coated groups effectively reduced the adhesion of both S. aureus and E. coli. In conclusion, combining SLA modification, argon plasma treatment, and rhSLPI coating provides enhanced effects. This combined approach significantly enhances osteoblast adhesion and mineralization while possessing antibacterial potential, which could be a promising strategy to improve implant success rates.