The impaired differentiation ability of resident cells and disordered immune microenvironment in periodontitis pose a huge challenge for bone regeneration. Herein, we construct a piezoelectric hydrogel to rescue the impaired osteogenic capability and rebuild the regenerative immune microenvironment through bioenergetic activation. Under local mechanical stress, the piezoelectric hydrogel generated piezopotential that initiates osteogenic differentiation of inflammatory periodontal ligament stem cells (PDLSCs) via modulating energy metabolism and promoting adenosine triphosphate (ATP) synthesis. Moreover, it also reshapes an anti-inflammatory and pro-regenerative niche through switching M1 macrophages to the M2 phenotype. The synergy of tilapia gelatin and piezoelectric stimulation enhances in situ regeneration in periodontal inflammatory defects of rats. These findings pave a new pathway for treating periodontitis and other immune-related bone defects through piezoelectric stimulation-enabled energy metabolism modulation and immunomodulation.
A wireless piezoelectric hydrogel was developed to generate electric signals effectively under various mechanical stresses.
The piezoelectric stimulation could energize impaired PDLSCs to osteogenic differentiation by boosting Δψ m.
The piezoelectric hydrogel rebuilt an anti-inflammatory and pro-regenerative niche by phenotypic switching of macrophages.
The piezoelectric hydrogel enabled a high-quality regeneration of impaired tissue in periodontal inflammatory defects.