Titanium-Based Piezoelectric Dual-Network Hydrogel Coatings for Bone Regeneration Enhancement

Titanium implants are not able to exhibit significant osseointegration effects due to their bioinert surfaces and mechanical mismatch. Extensive research has focused on modifying titanium surfaces with micro/nano-topography and bioactive factors to mimic biochemical microenvironments. However, replicating the bone endogenous electrical microenvironment to enhance osseointegration remains a challenge. Whitlockite (Ca₁₈Mg₂(HPO₄)₂(PO₄)₁₂, WH) is the second most abundant inorganic constituent in native bone, and it exhibits bioactive properties comparable to hydroxyapatite. It is remarkable that WH NPs subjected to high-temperature sintering demonstrate pronounced piezoelectric properties. In this work, a titanium-based composite piezoelectric hydrogel coating was developed by integrating sintered WH NPs with gelatin methacrylate (GelMA)-sodium alginate (SA) dual-network hydrogel matrix. This coating possessed a three-dimensional network structure conducive to cell adhesion and spreading, appropriate mechanical properties, biodegradability, and piezoelectricity. Under low-intensity pulsed ultrasound stimulation (LIPUS), this titanium-based piezoelectric hydrogel coating converted mechanical stresses into electrical signals, thereby restoring the electrical microenvironment at the site of bone defects. This coating effectively induced the osteogenic differentiation of BMSCs. It enhances the osseointegration of titanium implants through LIPUS-assisted piezoelectric stimulation.