Promoting bone regeneration with liquid crystal bone cement from a new perspective: Inhibiting BMSCs PANoptosis under aseptic inflammation

PANoptosis has become an important way to systematically analyses and address extensive crosstalk and common regulatory targets between different programmed cells death pathways. Focusing on the PANoptosis of bone marrow mesenchymal stem cells (BMSCs) induced by implants would be an encouraging way to improve cells survival and bone regeneration. In this study, we designed a liquid crystal hydrogel bone cement GelHap/TCLC, through phase state bionic to mimic the dynamic viscoelastic microenvironment of bone, to downregulate cells PANoptosis, wherein mouse monocyte-macrophages mouse macrophages (RAW264.7) and BMSCs were cocultured on the bone cement to simulate an immune-inflammatory state. Results showed that the liquid crystal hydrogels possessed a surface modulus of 80 f 6.62 kPa, close to the natural bone matrix. PANoptosis of BMSCs was reduced with cells survival rate of 90.7 f 2.3 %, which was higher than 83.1 f 1.7 % of nonliquid crystal GelHap and 72.9 f 2.9 % of commercial bone cement. Notably, the BMSCs PANoptosis executioners were inhibited obviously than the control. In addition, osteogenic differentiation in vitro and bone regeneration in vivo (BV/TV = 28.80 f 1.09 % at week 8) were promoted. This study bridges the gap between bone implants and BMSCs programmed death from a more systematic perspective, complements the liquid crystal state theory governing the fate of stem cell death in a broader sense, provides a class of biomimetic tissue engineering materials to solve the problem of BMSCs survival caused by aseptic inflammation induced by implants.