Cell microparticles loaded with pro-inflammatory factors and chloroquine collaborate with mechanical force to...

Malocclusion is regarded as a serious dental problem involving above 60 % populations worldwide. The main challenge for clinical orthodontic treatment lies in insufficient remodeling microenvironment, lack of active immune response and inadequate osteoclastic behavior, as mechanical application fails to trigger high-performance periodontal reconstruction. Regulation on macrophages is a promising method for strengthening tissue remodeling. Here, pro-inflammatory macrophage-derived microparticles loaded with chloroquine (CQ@PMMPs) are fabricated and integrated into a pH-responsive microneedle patch to precisely target at periodontal-resident macrophages for M1 polarization. In response to force-induced aseptic inflammation, local low-pH triggers degradation of microneedle and slow release of CQ@PMMPs, which activate macrophages to facilitate orthodontic force-induced periodontal remodeling and accelerated tooth movement through increasing the recruitment of monocytes and differentiation of monocytes into osteoclasts. Mechanistic exploration elucidates that encapsulated chloroquine in combination with pro-inflammatory cytokines in microparticles altogether promoted M1 macrophage polarization and subsequent osteoclastic activity mainly via MAPK signaling pathway. These specific functions of CQ@PMMPs contribute to collaborating and enhancing orthodontic force treatment, thus facilitating periodontal remodel and tooth movement acceleration. In summary, our results shed light on the local application of CQ@PMMPs as potential strategy for efficient orthodontic tooth movement.